A prevailing model of auditory processing in the brain seeks to describe the responses of neurons to sound as a function of neural circuitry. Understanding such circuitry is essential for understanding auditory processing, but auditory circuitry can be altered by neuromodulators like serotonin. Many of the neurons that provide serotonin to the auditory system, found in the midline dorsal raphe nucleus, have activity patterns that correspond to the sleep/wake cycle. This suggests that serotonin affects neural processing in ways that are dependent on behavioral state. Thus, knowing how serotonin affects auditory processing is important for understanding how the auditory system functions during behavior. A necessary first step towards attaining this understanding is to acquire more information on serotonergic effects at a cellular and systems level, which is the underlying goal of this application. Previous studies have examined the effects of externally applied serotonin in an important midbrain auditory nucleus that serves as a gateway in the auditory system, the inferior colliculus (IC). Serotonin has a broad range of effects in this nucleus. The diversity of serotonergic effects in the IC is likely to arise at least partly as a result of multiple types of serotonin receptors. The specific aims of this study are, therefore: 1) to characterize the involvement of different serotonin receptor types in serotonergic effects in the IC. This will be accomplished by using selective agonists and antagonists of serotonin receptors to mimic and block, respectively, the effects of locally applied serotonin. 2) A second aim is to determine whether serotonin receptors are endogenously activated in awake animals, as predicted by the firing patterns of dorsal raphe neurons. In other systems of the brain, the dissection of receptor mechanisms of serotonin has led to important insights into serotonin action on normal brain function and disease. In a similar vein, these experiments have long-term implications for understanding many of the auditory behaviors and pathologies in which serotonin is thought to play a role, including auditory gating, hyperacusis, and tinnitus. By proposing such basic research that may eventually contribute to quality of life, this application furthers the first goal of the Healthy People 2010 initiative. [unreadable] [unreadable]